Postsynaptic short‐chain neurotoxins from <i>Pseudonaja textilis</i>

Gong, Nanling; Armugam, Arunmozhiarasi; Jeyaseelan, Kandiah

doi:10.1046/j.1432-1327.1999.00800.x

Cited by 42 publications

(9 citation statements)

References 54 publications

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“…Type III α-neurotoxins were recovered from P. modesta, which was expected as they have previously been characterised from other Pseudonaja as well as Oxyuranus venoms [28,30,31]. Interestingly, they were also recovered from B. roperi , C. squamulosus, F. ornata and V. annulata , representing the first time this toxin type has been recovered from species outside the Pseudonaja / Oxyuranus clade.…”

Section: Resultssupporting

confidence: 60%

Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

Jackson

Sunagar

Undheim

et al. 2013

Toxins

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Despite the unparalleled diversity of venomous snakes in Australia, research has concentrated on a handful of medically significant species and even of these very few toxins have been fully sequenced. In this study, venom gland transcriptomes were sequenced from eleven species of small Australian elapid snakes, from eleven genera, spanning a broad phylogenetic range. The particularly large number of sequences obtained for three-finger toxin (3FTx) peptides allowed for robust reconstructions of their dynamic molecular evolutionary histories. We demonstrated that each species preferentially favoured different types of α-neurotoxic 3FTx, probably as a result of differing feeding ecologies. The three forms of α-neurotoxin [Type I (also known as (aka): short-chain), Type II (aka: long-chain) and Type III] not only adopted differential rates of evolution, but have also conserved a diversity of residues, presumably to potentiate prey-specific toxicity. Despite these differences, the different α-neurotoxin types were shown to accumulate mutations in similar regions of the protein, largely in the loops and structurally unimportant regions, highlighting the significant role of focal mutagenesis. We theorize that this phenomenon not only affects toxin potency or specificity, but also generates necessary variation for preventing/delaying prey animals from acquiring venom-resistance. This study also recovered the first full-length sequences for multimeric phospholipase A2 (PLA2) ‘taipoxin/paradoxin’ subunits from non-Oxyuranus species, confirming the early recruitment of this extremely potent neurotoxin complex to the venom arsenal of Australian elapid snakes. We also recovered the first natriuretic peptides from an elapid that lack the derived C-terminal tail and resemble the plesiotypic form (ancestral character state) found in viper venoms. This provides supporting evidence for a single early recruitment of natriuretic peptides into snake venoms. Novel forms of kunitz and waprin peptides were recovered, including dual domain kunitz-kunitz precursors and the first kunitz-waprin hybrid precursors from elapid snakes. The novel sequences recovered in this study reveal that the huge diversity of unstudied venomous Australian snakes are of considerable interest not only for the investigation of venom and whole organism evolution but also represent an untapped bioresource in the search for novel compounds for use in drug design and development.

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Section: Resultssupporting

confidence: 60%

Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

Jackson

Sunagar

Undheim

et al. 2013

Toxins

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“…Out of 70 such clones, five short‐chain neurotoxin genes were identified, with an almost equal frequency (20%) of appearance for each of them. These genes represented the mRNAs [3] identified in the venom gland of the same snake. Thus, they are functional and do not represent any pseudogene(s).…”

Section: Resultsmentioning

confidence: 99%

“…Pseudonaja textilis , a common brown snake found in the farmlands of eastern Australia, is one of the most poisonous elapids in the world. A new group of short‐chain neurotoxins from P. textilis were identified and characterized by us recently [3]. They bind specifically to nicotinic acetylcholine receptors at neuromuscular junction, as expected for any short‐chain neurotoxins.…”

Section: Introductionmentioning

confidence: 95%

Molecular cloning, characterization and evolution of the gene encoding a new group of short‐chain α‐neurotoxins in an Australian elapid, Pseudonaja textilis

2000

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The structure and organization of five genes responsible for the synthesis of six isoforms of short-chain K K-neurotoxins in Pseudonaja textilis venom are reported in this paper. This also forms the first report which describes the synthesis of two neurotoxin mRNA variants from one of these genes (Pt-sntx1) as a result of alternative splicing. Each gene consists of three exons which are separated by two introns and each has a functional promoter. The promoter activity was confirmed by both CAT assay and Real-Time PCR. A transcription initiation site, two putative TATA boxes, one CCAAT box and the transcription factor binding consensus sites for AP-1, GATA-2, c/EBPb were identified in the 5P P non-coding region of each gene. Phylogenetic analysis showed that these five genes from P. textilis constituted a distinct group which has evolved by gene duplication followed by accelerated evolution from an ancestral gene.z 2000 Federation of European Biochemical Societies.

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“…This expanded target potential makes them extremely useful for prey paralysis and probably explains the greater influence of positive selection on this type of 3FTx. Type III α-ntx has been demonstrated to exhibit activities similar to that of Type I α-ntxs, but at a lower potency, in experiments conducted on mice [28]. Prey-specific toxicity has been demonstrated in a variety of α-ntxs [20,21,82].…”

Section: Discussionmentioning

confidence: 99%

Three-Fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of Snake Venom Toxins

Sunagar

Jackson

Undheim

et al. 2013

Toxins

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Three-finger toxins (3FTx) represent one of the most abundantly secreted and potently toxic components of colubrid (Colubridae), elapid (Elapidae) and psammophid (Psammophiinae subfamily of the Lamprophidae) snake venom arsenal. Despite their conserved structural similarity, they perform a diversity of biological functions. Although they are theorised to undergo adaptive evolution, the underlying diversification mechanisms remain elusive. Here, we report the molecular evolution of different 3FTx functional forms and show that positively selected point mutations have driven the rapid evolution and diversification of 3FTx. These diversification events not only correlate with the evolution of advanced venom delivery systems (VDS) in Caenophidia, but in particular the explosive diversification of the clade subsequent to the evolution of a high pressure, hollow-fanged VDS in elapids, highlighting the significant role of these toxins in the evolution of advanced snakes. We show that Type I, II and III α-neurotoxins have evolved with extreme rapidity under the influence of positive selection. We also show that novel Oxyuranus/Pseudonaja Type II forms lacking the apotypic loop-2 stabilising cysteine doublet characteristic of Type II forms are not phylogenetically basal in relation to other Type IIs as previously thought, but are the result of secondary loss of these apotypic cysteines on at least three separate occasions. Not all 3FTxs have evolved rapidly: κ-neurotoxins, which form non-covalently associated heterodimers, have experienced a relatively weaker influence of diversifying selection; while cytotoxic 3FTx, with their functional sites, dispersed over 40% of the molecular surface, have been extremely constrained by negative selection. We show that the a previous theory of 3FTx molecular evolution (termed ASSET) is evolutionarily implausible and cannot account for the considerable variation observed in very short segments of 3FTx. Instead, we propose a theory of Rapid Accumulation of Variations in Exposed Residues (RAVER) to illustrate the significance of point mutations, guided by focal mutagenesis and positive selection in the evolution and diversification of 3FTx.

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Postsynaptic short‐chain neurotoxins from Pseudonaja textilis

Cited by 42 publications

References 54 publications

Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

Venom Down Under: Dynamic Evolution of Australian Elapid Snake Toxins

Molecular cloning, characterization and evolution of the gene encoding a new group of short‐chain α‐neurotoxins in an Australian elapid, Pseudonaja textilis

Three-Fingered RAVERs: Rapid Accumulation of Variations in Exposed Residues of Snake Venom Toxins

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